Design and synthesis of pyrazole/isoxazole linked arylcinnamides as tubulin polymerization inhibitors and potential antiproliferative agents.
Org Biomol Chem
; 13(40): 10162-78, 2015 Oct 28.
Article
em En
| MEDLINE
| ID: mdl-26303171
ABSTRACT
As pyrazole and isoxazole based derivatives are well-known for displaying a considerable biological profile, an attempt has been made to unravel their cytotoxic potential. In this context, a number of pyrazole/isoxazole linked arylcinnamide conjugates (15a-o and 21a-n) have been synthesized by employing a straight forward route. The basic structure comprised three ring scaffolds (A, B and C) methoxyphenyl rings as A and C rings and a five membered heterocyclic ring (pyrazole or isoxazole) as the B-ring. To achieve clear understanding, these derivatives are categorized as pyrazole-phenylcinnamides (PP) and isoxazole-phenylcinnamides (IP). These compounds have been evaluated for their ability to inhibit the growth of various human cancer cell lines such as HeLa, DU-145, A549 and MDA-MB231 and most of them exhibit considerable cytotoxic effects. Some of them like 15a, 15b, 15e, 15i and 15l exhibit promising cytotoxicity in HeLa cells (IC50 = 0.4, 1.8, 1.2, 2.7 and 1.7 µM). Amongst them 15a, 15b and 15e were taken up for detailed biological studies, they were found to arrest the cells in the G2/M phase of the cell cycle. Moreover, they were investigated for their effect on the microtubular cytoskeletal system by using a tubulin polymerization assay, immunofluroscence and molecular docking studies; interestingly they demonstrate a significant inhibition of tubulin polymerization.
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Base de dados:
MEDLINE
Assunto principal:
Pirazóis
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Tubulina (Proteína)
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Desenho de Fármacos
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Cinamatos
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Moduladores de Tubulina
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Isoxazóis
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Antineoplásicos
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article